The long-term goal of this project is to identify early temperamental/emotional precursors of major depressive disorder (MDD) and to trace the pathways from early temperamental emotionality to the development of MDD in order to provide a basis for the early identification of children at risk and for understanding how and when to intervene to prevent the onset or escalation of the disorder. This is a continuation of a longitudinal study of a large community sample of children (N = 559) who completed intensive assessments at ages 3 and 6, and whom we seek to re-evaluate at age 9. The goal of the current proposal is to map the pathways from early low positive emotionality (PE) and high negative emotionality (NE) to a set of intermediate outcomes in middle childhood that may serve as more proximal risk factors that set the stage for, and mediate, the surge in depressive disorders expected in adolescence and young adulthood. We hypothesize that low PE and high NE in early childhood will predict abnormalities in three important domains in middle childhood that may constitute intermediate outcomes on pathways to the development of MDD: (1) abnormalities in the processing of emotional information, assessed using behavioral and electrocortical laboratory paradigms;(2) one form of limbic hypothalamic-pituitary-adrenal axis dysregulation - elevated morning cortisol levels;and (3) subclinical depressive symptoms and anxiety symptoms/disorders. In addition, we will explore whether these intermediate outcomes differ as a function of sex and are associated with individual differences in the early phase of pubertal maturation (adrenarche). Finally, we will test the hypothesis that associations of early genetic and familial risk factors with emotional processing biases, elevated morning cortisol, and depressive and anxiety symptoms in middle childhood are mediated by early temperamental emotionality. PUBLIC HEALTH RELEVANCE: The depressive disorders are highly prevalent and associated with significant mortality, morbidity, and economic costs. This project seeks to identify early behavioral precursors/risk factors for depression and understand the neurobiological and psychosocial processes through which these early manifestations develop into clinically significant disorders. This will contribute to understanding when and how to intervene in order to prevent the disorder and/or its progression.